metabolic bone disease in reptiles and anphibians

09/04/2015 Metabolic Bone Disease in Herpetoculture | Christina Miller

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Would you have noticed the subtle early signs of NSHP in this

Leopard Gecko (Eublepharis macularius)? The owners

certainly didn’t.

Metabolic Bone Diseases inReptiles and Amphibians | CalciumBalance

Authored by: Christina Miller CAHT/RVT, RLAT, BSc

MBD in HerpetocultureCaptive reptiles and amphibians are subject to a somewhat unique situation. Unlike our mammalian

companions, they’re highly dependent on their captive environment for their most basic physiology to

function, making good husbandry the key to maintaining healthy companions. One of the most common

health problems we see in captive herps relates to calcium metabolism:

The infamous “metabolic bone diseases,” often abbreviated as MBD in both lay

and professional literature.

I feel this is a suitable topic to start with in what will be

a series of health and medical columns, as it’s (in my

opinion) one of the saddest syndromes we treat in

captive herps. It’s entirely preventable in all but the

most obscure of cases, and metabolic bone diseases

essentially do not occur in wild animals. Often, early

clinical signs are subtle and go unnoticed by most

hobbyists. Prevention at the level of diagnosing

husbandry errors before they promote a disease

process is key (and that applies to all husbandry-

related pathologies in captive herps). My goal, is to

give our readers a basic understanding of the

complexities of this disease process (and others in the

future), and how to apply this understanding to your

husbandry techniques.

This subject is of course very complex. In fact, “metabolic bone disease” does not actually refer to one

pathology, but a series of syndromes that affect bone form and function (Mader 2006). The most

prevalent form of metabolic bone disease that we see in captive herps is nutritional secondary

hyperparathyroidism (NSHP- because it’s really quite a mouthful when you say it out loud). Before we

delve into the meaty medical and husbandry stuff, understanding the bodily processes that are involved

in using dietary calcium is the first step. There are a lot of intricate details to calcium metabolism, and

just because a herp is getting calcium in their diet, that does not necessarily mean that they can use it

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appropriately.

Calcium and Reptile RelationshipsBack to basics: Calcium in the body

Calcium, simplified, is an element in our diets, important for the health of bones, teeth, and muscles. It’s

a major component in the structure of both bones and teeth, contributing to the mineral-like rigidity of

these body parts. It’s also heavily involved in cellular signaling and blood clotting (Wedekind et al. 2010).

The most prominent effects of problems with calcium metabolism in our captive herps involves first the

structural component of the skeleton, and second the ability to maintain cellular signaling.

Calcium in our bones and teeth (about 99% of the body’s calcium) is in flux with the calcium in our blood

(the remaining 1%) (Wedekind et al. 2010). While we tend to think of our skeletons as mostly inert and

unchanging after we’ve reached adulthood, bones are constantly being broken down and built back up

again by a series of cells called osteoclasts and osteoblasts. Osteoblasts create new bone out of

calcium, phosphorus, and other components, and once they’ve become trapped in their own mineral

matrix they are called osteocytes. Osteocytes can transform to break down bone (now called

osteoclasts) so that bone can be remodeled and those components can re-enter the bloodstream

(Colville and Bassert 2002).

While this seems like a lot of detail to go into, I assure you understanding the

skeleton is not a static, unchanging structure is an important concept.

Many cellular signals rely on calcium moving in and out of cells, usually involving proteins that act as

pumps to move calcium across the cell membrane (Alberts et al. 2008). The most relevant cell signaling

for our purposes involves muscle contractions, both voluntary (used for conscious movements) and

involuntary (such as cardiac muscles responsible for maintaining blood flow). In short, calcium is

stimulated to enter the involved cells by an electrical stimulus (called an action potential) from the central

nervous system. This initiates a chain reaction in submicroscopic muscle fibre structures that results in

muscle contraction (Colville and Bassert 2002). Without adequate levels of calcium in the blood,

problems with muscle contraction occur (as well as with the uncountable other cell processes involving

calcium).

Calcium homeostasis

As mentioned above, calcium moves back and forth between bones and the bloodstream, and these

processes are very tightly controlled by multiple organs. First and foremost, the concentration of calcium

in the blood is the major driver of all of the following processes. When calcium is used for bone

building/remodeling, in signaling molecules (like neurotransmitters), and some cellular processes, this

depletes some of the free calcium in the blood (Colville and Bassert 2002). When the ionized calcium

concentration drops below a specific concentration, the parathyroid gland (located in the neck of all

vertebrates except fish) reacts by secreting parathyroid hormone (Wedekind et al. 2010).

Hypercalcemia in Reptiles

Parathyroid hormone, which we’ll abbreviate as PTH, works several ways to correct hypocalcemia (see

Figure 2 for a diagram version of the following):

1. PTH induces osteoclastic activity in bone tissue by binding to osteoblasts and causes them to

transform into osteoclasts. Osteoclasts initiate bone resorption, which release stored calcium (and

phosphorus in the form of phosphate) into the bloodstream.



Calcium Homeostasis in Reptiles

2. PTH acts on the kidneys to recuperate calcium (as well as magnesium) that would have been

excreted in the urine, and increases phosphate excretion into the urine. (Calcium and phosphorus

have a close relationship, but we’ll explore that topic more, later.)

3. PTH initiates another cell signaling process in the kidneys to help absorb calcium from the diet.

This part involves the vitamin D3 metabolism process, which we’ll touch on soon. Essentially, the

intestines receive a signal to let more calcium into the bloodstream from food in the animal’s gut.

Note that there is always some passive absorption of dietary calcium, but it alone is not adequate

to correct hypocalcemia (Wedekind et al. 2010).

If PTH starts this sequence but blood calcium cannot

reach adequate levels, the parathyroid gland

continues to be stimulated to produce PTH, resulting

in a negative feedback loop that will not stop until the

hypocalcemia has been corrected.

If and when blood calcium levels rise too high

(hypercalcemia), the thyroid gland, found next to the

parathyroid glands will release the hormone

calcitonin. Calcitonin causes the opposite of PTH’s

functions (refer again to Figure 2 to see this in

diagram form):

1. Calcitonin inhibits osteoclastic activity, slowing

bone resorption. It also stimulates osteoblastic

activity, causing calcium to be redeposited into

bone tissue.

2. Calcitonin inhibits calcium resorption in the kidneys, causing more calcium to be excreted in the

animal’s urine. However, it copies PTH in that it also inhibits phosphate resorption, so that more

phosphates are also excreted in the urine.

3. Finally, it inhibits calcium absorption from food in the intestines (Colville and Bassert 2002).

Phosphorus and Calcium

Phosphorus and calcium are intricately linked in nutrition. Phosphorus, like calcium, makes up a large

structural component of teeth and bones, so when osteoclasts initiate bone resorption there is release of

phosphorus in addition to calcium into the bloodstream (Colville and Bassert 2002), and recall that PTH

will stimulate the kidneys to excrete more phosphates to avoid phosphorus levels from climbing too high.

Hyperphosphatemia (high blood levels of phosphorus) is dangerous. Chronic hyperphosphatemia leads

to soft tissue mineralization, among other problems (Thrall et al. 2004).

These two nutrients like to stay within certain proportions of each other in the bloodstream; there exists a

relationship between calcium and phosphorus concentrations, and the pH of the blood. When too much

phosphorus is absorbed from the digestive system into the bloodstream, the calcium in the bloodstream

declines in relation to the phosphorus as it’s “forced” to precipitate as calcium phosphate (Thrall et al.

2004). Not only are the total amounts of calcium and phosphorus in the diet important, but their

proportions to each other is also critical when it comes to calcium balance. The calcium-to-phosphorus

ratio is critical in diet assessment (Wedekind et al. 2010), and we’ll touch more on this topic later.

So, we’ve seen that the body runs a pretty tight ship when it comes to calcium and phosphorus. It has

ways to regulate how much calcium is in the bloodstream through those two hormones, PTH and

calcitonin. The main way the body replenishes used up calcium (and any nutrients) is through the diet. If

an animal is provided with a calcium-deficient diet, then they will be unable to replenish that lost calcium.



Basking isn’t just for thermoregulation. ThisInland Bearded Dragon (Pogona vitticeps) isbasking under both a heat lamp and a UV-B

producing bulb so that he may createendogenous vitamin D3.

But, as noted above, there’s another key factor in calcium metabolism that we still need to explore:

Vitamin D3.

D3: The “sunshine vitamin”

In response to low blood calcium levels, PTH signals though a series of reactions to the intestines to start

absorbing more calcium from food in the animal’s gut. PTH signals to the kidneys to initiate the

absorption process, but this is hardly where the story of vitamin D3 begins.

This process is simplified in some species. They eat another

animal that already contains pre-formed vitamin D3 (also called

cholecalciferol) that is transported to the liver and transformed

into calcidiol (a prohormone). When the kidneys are stimulated by

PTH, they start to convert calcidiol into calcitriol (a hormone),

which is the active form that signals to the intestines to start

absorbing dietary calcium (Colville and Bassert 2002). Note that

all of these compounds have alternate names in the literature, as

well as chemical names. I’ve included an appendix (Appendix 1)

for those who are interested in case you happen to see these

synonyms in the literature.

In most species, the process is a little more complicated. Many

animals synthesize their own vitamin D3 in the skin in response to

sunlight, which is why D3 is often called the sunshine vitamin.

Previtamin D3, found in the skin, reacts to sunlight and forms D3,

or cholecalciferol (Colville and Bassert 2002). The process then

continues as above. Sometimes this process is complimentary to

what’s absorbed from the diet, but in some species this is their

only source of vitamin D3.

With captive herps, this is where many of our problems occur. We know from trial and error in

herpetoculture that many species require an aspect of sunlight, ultraviolet-B radiation (UV-B), in order to

make their own vitamin D3. Failure to provide UV-B lighting results in the animal not being able to use

calcium in their diet, which leads to metabolic disturbances.

Calcium Absorption in Reptiles

Linking physiology to disease

The above processes are a lot to digest (no pun intended). Let’s break down some common scenarios

that occur in captivity, and relate pathology to physiology:

There is not enough available calcium in the diet. This occurs either when the animal’s

diet simply contains insufficient amounts of calcium, or the calcium in the diet has a poor

bioavailability.The first scenario is simple: Not enough calcium. This occurs when an animal is

being fed primarily calcium-poor prey items or plants. Insectivores, for example, tend to suffer when

their insect prey is not gut-loaded and/or dusted within calcium, as most insects have a naturally

low calcium content (Donoghue 2006).

The second scenario involving calcium bioavailability can be quite variable, and to understand this

we need to take a detour into some general food science. The bioavailability of a nutrient (be it

calcium, a carbohydrate, zinc, a protein, etc.) is evaluated by how much of that nutrient is absorbed

from a food and is transported unchanged into the bloodstream to be used by the body (LPI 2014).



For example, calcium carbonate, the most common form of calcium in reptile and amphibians

powdered supplements, is less bioavailable than calcium citrate, another form of calcium

supplement (Hanzlik et al. 2005). This means that if the same amount of each supplement were

ingested by two separate animals, the animal who ate the calcium citrate would absorb more

useable calcium compared to the animal that ate the calcium carbonate. This of course does not

mean that calcium carbonate is a poor choice for supplements, but this aspect of any nutrient is

important when assessing diets.Furthermore, the presence of other foods in the diet can reduce

how much calcium is being absorbed into the bloodstream. Calcium antinutrients are a loosely-

defined group of naturally-occurring chemicals found in many common fruits and vegetables. They

bind to calcium in the digestive tract, and stop it from being absorbed by the body. Common

examples include oxalic acid and phytic acid (sometimes referred to as oxalates and phytates),

which are chemicals found in many vegetables that are commonly eaten by both people and pet

herbivorous or omnivorous reptiles. Both compounds will bind to dietary calcium and form

compounds that will not be absorbed, but will be excreted instead (Charles 1992, Donoghue 2006,

Guéguen and Pointillart 2000). A person’s diet tends to be quite varied, so these antinutrients will

likely have a negligible effect. In a reptile that is fed a limited variety of foods, these antinutrients

are encountered more commonly and can have a serious impact on how much calcium is absorbed

from the diet.In either scenario, there is just not enough calcium being transported from the

digestive tract through the bloodstream to the target organs. The body uses the calcium that is

absorbed and bioavailable, but will run short when trying to reach its target blood concentration of

calcium, and will resort to depleting more and more calcium from the bone “storehouse.” This

eventually results in a notable loss of bone density.

The dietary ratio of calcium to phosphorus (Ca:P) is incorrect.Reptiles and amphibians

generally need a dietary Ca:P of 1.5-2.0:1.0 (one-and-a-half to twice as much calcium compared to

phosphorus). Recall that when too much phosphorus relative to calcium is absorbed it will cause a

drop in blood calcium, which initiates the sequence of PTH trying to bring the calcium concentration

back to a normal level.

The animal does not ingest or cannot make enough of its own vitamin D3. Recall that this

vitamin is essential in the process of absorbing calcium from the diet to correct hypocalcemia. Many

species of reptile and amphibian rely heavily on sunlight to produce their own vitamin D3 rather

than obtain all of their needed D3 from their diet (Ferguson et al. 2003), and some species cannot

absorb dietary D3 and completely rely on endogenous vitamin D3 production, including the Green

Iguana,Iguana iguana (Allen and Oftedal 2003, Bernard et al. 1991).True dietary vitamin D3

deficiencies are rare. Most carnivores tend to be fed whole prey, which is (or was) a healthy animal

in itself that was meeting its own D3 quotas. Carnivores that are only fed select portions of a whole

animal, such as those being fed only muscle meat, are more susceptible to this kind of problem

(Donoghue 2006).The most common scenario for vitamin D3 deficiency involves failing to provide

broad spectrum lighting that includes UV-B radiation, or not using these devices appropriately.

Let’s revisit NSHP, or nutritional secondary hyperparathyroidism, and why this form of metabolic bone

disease applies to most husbandry errors. We’ve seen above that the parathyroid gland is heavily

involved in regulating blood calcium levels; hyperparathyroidism refers to excessive activity of this gland.

This syndrome occurs secondary to nutritional factors, such as calcium, phosphorus, and vitamin D3

intake, which is why this disease is considered nutritional.

Clearly, metabolic bone diseases are anything but simple. Next, we will explore how these nutritional and

husbandry problems develop into disease, how veterinarians will treat it, and what we can do to prevent

it.



Appendix 1: Synonyms for forms of vitamin D3

Compound Synonyms (not an exhaustive list)

Vitamin D3 Cholecalciferol, calciol

Previtamin D3 Provitamin D3, 7-Dehydrocholesterol

Calcidiol Calcifediol, hydroxycholecalciferol, 25-hydroxyvitamin D3

Calcitriol 1,25-dihydroxyvitamin D3

PART 2: Metabolic Bone Disease | Pathophysiology and Clinical Signs

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Bernard, J, O Oftedal, P Barbosa, C Mathias, M Allen, S Citino, D Ullrey, R Montali. 1991. “The response

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http://reptileapartment.com/metabolic-bone-disease-in-reptiles-part-2-pathophysiology-and-clinical-signs/



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